The broad goal of the research described in this proposal is to understand (i) how developing and regenerating chemosensory nerves navigate their paths to their appropriate targets; (ii) how, when they reach the targets, they stop growing and (iii) how they alter their gene expression from a growth mode to a mature mode in which they form a functional relationship with the target. In both the taste and the olfactory systems we suggest that both the environment through which the nerve growth and the target structures provide signals that regulate the behavior of growing and mature nerve. These signals are likely to include navigational guidance cues, "stop growth" signals, and signals that induce changes in gene expression. In the rat tongue, 2 sensory nerves, the lingual proper (LP) branch of the trigeminal, and the chorda tympani (CT) provide innervation to fungiform papillae. During development they enter the tongue simultaneously but are directed to different targets. The CT innervates the apices of the fungiform papillae whereas the LP innervates other regions of these structures, as well as the remainder of the anterior tongue. We propose to identify the navigational signals directing these nerves to different targets in the fungiform papilla by; (1) mapping the distribution of extracellular matrix (ECM) molecules that might promote (or inhibit) nerve growth; (2) identifying surface molecules on growing and regenerating sensory nerves in the tongue that might act as receptors of signals present in the environment or on the synaptic target; (3) identifying positive and negative tropic signals and stop signals for axonal growth in the developing tongue; (4) identifying signals that alter gene expression in gustatory neurons. The taste bud containing circumvallate papilla is innervated by the glossopharyngeal nerve. Because gustatory and somatosensory nerves in the glossopharyngeal nerve arise from two distinct ganglia in the rat we will also be able to examine some of these issues in the innervation o the circumvallate papilla. In the olfactory system we propose (1) to identify the "stop growth" signal for olfactory axons; (2) to identify soluble or membrane-associated bulbar signals that act to alter gene expression in olfactory neurons. Both in vivo and in vitro methods will be used.